The development of aquaculture, especially in mariculture, contributes to satisfy the increasing demand for aquatic food, but it also faces serious socio-economic and environmental issues. This is also consistent with aquaculture in the Southern Central Region (SCR), Vietnam. The paper conducted to evaluate the mariculture status and activities by questionnaire interviews of 255 mariculture stakeholders (cages/rafts owners) and their challenges by in-depth interviews of 16 aquaculture managing officers at eight provinces in SCR, 2018-2019. The results showed an assessment of the current status of mariculture, SWOT (strengths, weaknesses, opportunities, and threats) analysis, and orientation strategies of mariculture development. For a long time, the aquaculture area has not varied considerably, and mainly distributed in inland, coastal and off-coastal waters, almost it is not implemented in the open sea yet. Mariculture was also challenged by various concerned issues: various types of mariculture and species, small scale, outdated traditional technology, and labor force with fair practices in mariculture. Almost them are made the challenge for aquaculture expansion and implementation in open seas. Moreover, capital sources and credit access of stakeholders, and enterprise's investment are key factors to develop offshore mariculture. Based on the results of SWOT analysis, five strategies are proposed for sustainable development of mariculture in the SCR, as well as to meet the objectives of Vietnam's mariculture strategy. It is noted that when developing mariculture on an industrial scale to increase commercial products, the small- and medium-scale ones are vulnerable, so expansion and development of mariculture should be combined with the creation of job opportunities, reduction of poverty alleviation and economic growth and sustainability.